Summary
With the exponential growth of the human population and industrial developments, research on renewable energy resources is required to alleviate environmental and economic impacts caused by ...the consumption of fossil fuels. In this study, we present a synthetic biological application of a wood forming tissue‐specific bicistronic gene expression system to improve both the quantity and quality of woody biomass to minimize undesirable growth penalties. Our transgenic poplars, designed to express both PdGA20ox1 (a GA20‐oxidase from Pinus densiflora producing bioactive gibberellin, GA) and PtrMYB221 (a MYB transcription factor negatively regulating lignin biosynthesis) under the developing xylem (DX) tissue‐specific promoter (i.e., DX15::PdGA20ox1‐2A‐PtrMYB221 poplar), resulted in a 2‐fold increase in biomass quantity compared to wild‐type (WT), without undesirable growth defects. A similar phenotype was observed in transgenic Arabidopsis plants harboring the same gene constructs. These phenotypic consequences were further verified in the field experiments. Importantly, our transgenic poplars exhibited an improved quality of biomass with reduced lignin content (~16.0 wt%) but increased holocellulose content (~6.6 wt%). Furthermore, the saccharification efficiency of our transgenic poplar increased significantly by up to 8%. Our results demonstrate that the controlled production of both GA and a secondary wall modifying regulator in the same spatio‐temporal manner can be utilized as an efficient biotechnological tool for producing the desired multi‐purpose woody biomass.
Time‐resolved x‐ray liquidography (TRXL) is a powerful technique to study molecular structural dynamics in the solution phase. Typically, a TRXL experiment is conducted during limited beamtime at a ...beamline of a synchrotron or an x‐ray free‐electron laser, demanding a proper design and careful planning. In this regard, the optimal q range needs to be determined to find the optimal x‐ray energy and sample‐to‐detector distance. For such purpose, here, we present effective ways to quantify the sensitivity of the TRXL data as a function of q to various factors such as the atomic positions, internuclear distances, solvent cage, and bulk solvent. The developed approaches are also applicable to other types of time‐resolved diffraction, such as ultrafast electron diffraction.
We present effective means to quantify the sensitivity of time‐resolved x‐ray liquidography (TRXL) data to the molecular structure, especially to the position of each atom and to the pairwise distance between the atoms, as a function of the magnitude of the momentum transfer vector (q). The developed approaches allow for systematically designing and planning the TRXL experiments, which are typically conducted during limited beamtime at a beamline.
Previous studies found that patients with an acute coronary syndrome (ACS) due to occlusion of the left circumflex (LC) coronary artery often present without ST-elevation, leading to a delay in ...diagnosis and revascularization, a larger infarct size, and a worse prognosis. In this subgroup analysis of the ELISA-3 study (early or late intervention in high-risk non–ST-segment elevation acute coronary syndromes NSTE-ACS) incidence, characteristics and prognosis of LC-related NSTE-ACS was investigated, and the outcome of early versus late invasive strategy was compared. In 383 of 542 patients the culprit vessel could be identified, with the LC artery in 112 (29%) of them. Patients with LC-related ACS had more often single vessel disease and underwent percutaneous coronary intervention more and CABG less frequently. The primary end point of the combined incidences of death, myocardial infarction, and recurrent ischemia at 30-day follow-up occurred in 9.0% of LC versus 16.5% of non–LC-related ACS (p = 0.057). Enzymatic infarct size and incidence of bleeding were comparable. Of patients with LC-related ACS, 62 were assigned to an early and 50 to a late invasive treatment with a median time from admission to angiography of 5.5 and 65.7 hours, respectively. The primary end point occurred in 9.7% and 8.0%, respectively (p = 1.00) with comparable enzymatic infarct size and bleeding. In conclusion, no significant differences in outcome were found between patients with an LC- and a non–LC-related NSTE-ACS. In LC-related NSTE-ACS, angiography within 12 hours of admission is feasible but not superior to angiography after more than 48 hours.
Summary
With the exponential growth of the human population and industrial developments, research on renewable energy resources is required to alleviate environmental and economic impacts caused by ...the consumption of fossil fuels. In this study, we present a synthetic biological application of a wood forming tissue‐specific bicistronic gene expression system to improve both the quantity and quality of woody biomass to minimize undesirable growth penalties. Our transgenic poplars, designed to express both
Pd
GA
20ox1
(a
GA
20‐oxidase from
Pinus densiflora
producing bioactive gibberellin,
GA
) and
Ptr
MYB
221
(a
MYB
transcription factor negatively regulating lignin biosynthesis) under the developing xylem (
DX
) tissue‐specific promoter (i.e.,
DX
15::Pd
GA
20ox1‐2A‐Ptr
MYB
221
poplar), resulted in a 2‐fold increase in biomass quantity compared to wild‐type (
WT
), without undesirable growth defects. A similar phenotype was observed in transgenic Arabidopsis plants harboring the same gene constructs. These phenotypic consequences were further verified in the field experiments. Importantly, our transgenic poplars exhibited an improved quality of biomass with reduced lignin content (~16.0 wt%) but increased holocellulose content (~6.6 wt%). Furthermore, the saccharification efficiency of our transgenic poplar increased significantly by up to 8%. Our results demonstrate that the controlled production of both
GA
and a secondary wall modifying regulator in the same spatio‐temporal manner can be utilized as an efficient biotechnological tool for producing the desired multi‐purpose woody biomass.
Background With advances in peripheral artery disease ( PAD ) treatments such as endovascular treatment ( EVT ), personalized patient assessment is important. Data on sex differences in clinical ...outcome for PAD patients undergoing EVT have been limited, and studies have produced conflicting results. This study sought to compare midterm clinical outcomes between women and men in a large population of patients with PAD undergoing EVT . Methods and Results The K- VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease) registry is a nationwide, multicenter, observational study that includes 3073 PAD patients undergoing EVT . The study population was divided into men (n=2523) and women (n=550). The primary outcome was a composite of death, myocardial infarction, and major amputation; the secondary outcome included major adverse limb events. Women had more comorbidities and more severe and complex target lesions than men. Women showed higher rates of death, myocardial infarction, or major amputation than men (14.8% versus 9.8%, adjusted hazard ratio 1.350, 95% CI 1.017-1.792, P=0.038), and higher rates of major adverse limb events (19.9% versus 14.5%, adjusted hazard ratio 1.301, 95% CI 1.014-1.670, P=0.039) and procedural complications (10.2% versus 5.9%, P<0.001) based on multivariable analysis. In patients with claudication, the primary outcome incidence was significantly higher in women (hazard ratio 2.088, 95% CI 1.421-3.068, P<0.001). In contrast, there was no significant difference in primary outcome for patients with critical limb ischemia between the 2 groups (hazard ratio 1.164, 95% CI 0.800-1.694, P=0.426). A significant interaction ( P=0.035) between patient presentation and outcome was observed. Conclusions In a large population of patients with PAD undergoing EVT , women had higher rates of death, myocardial infarction, or major amputation than men and higher rates of complex lesions, procedural complications, and limb-specific adverse events.
Despite increased awareness and availability of genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome for over 20 years, there is still significant underuse of cascade genetic ...testing among at-risk relatives. This scoping review synthesized evidence regarding psychosocial barriers and facilitators of family communication and/or uptake of cascade genetic testing in relatives from HBOC families. Search terms included ‘hereditary breast and ovarian cancer’ and ‘cascade genetic testing’ for studies published from 2012–2022. Through searching common databases, and manual search of references, 480 studies were identified after excluding duplications. Each article was reviewed by two researchers independently and 20 studies were included in the final analysis. CASP, RoBANS 2.0, RoB 2.0, and MMAT were used to assess the quality of included studies. A convergent data synthesis method was used to integrate evidence from quantitative and narrative data into categories and subcategories. Evidence points to 3 categories and 12 subcategories of psychosocial barriers and facilitators for cascade testing: (1) facilitators (belief in health protection and prevention; family closeness; decisional empowerment; family support, sense of responsibility; self-efficacy; supportive health professionals); (2) bidirectional concepts (information; perception of genetic/cancer consequences; negative emotions and attitude); and (3) barriers (negative reactions from family and negative family dynamics). Healthcare providers need to systematically evaluate these psychosocial factors, strengthen facilitators and alleviate barriers to promote informed decision-making for communication of genetic test results and uptake of genetic testing. Bidirectional factors merit special consideration and tailored approaches, as they can potentially have a positive or negative influence on family communication and uptake of genetic testing.
Hereditary breast and ovarian cancer and Lynch syndrome are associated with increased lifetime risk for common cancers. Offering cascade genetic testing to cancer-free relatives of individuals with ...HBOC or LS is a public health intervention for cancer prevention. Yet, little is known about the utility and value of information gained from cascade testing. This paper discusses ELSI encountered during the implementation of cascade testing in three countries with national healthcare systems: Switzerland, Korea, and Israel.
A workshop presented at the 5th International ELSI Congress discussed implementation of cascade testing in the three countries based on exchange of data and experiences from the international CASCADE cohort.
Analyses focused on models of accessing genetic services (clinic-based versus population-based screening), and models of initiating cascade testing (patient-mediated dissemination versus provider-mediated dissemination of testing results to relatives). The legal framework of each country, organization of the healthcare system, and socio-cultural norms determined the utility and value of genetic information gained from cascade testing.
The juxtaposition of individual versus public health interests generates significant ELSI controversies associated with cascade testing, which compromise access to genetic services and the utility and value of genetic information, despite national healthcare/universal coverage.
Accumulating data support the involvement of the serotonin (5-hydroxytryptamine 5-HT) system in the pathophysiology of chronic fatigue syndrome. Neuropharmacologic studies point to a hyperactive 5-HT ...system, and open-label treatment studies with 5-HT(3) receptor antagonists have shown promising results. In this randomized controlled clinical trial, the effect of ondansetron, a 5-HT(3) receptor antagonist, was assessed on fatigue severity and functional impairment in adult patients with chronic fatigue syndrome.
A randomized, placebo-controlled, double-blind clinical trial was conducted at Radboud University Nijmegen Medical Centre, The Netherlands. Sixty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome and who were free from current psychiatric comorbidity participated in the clinical trial. Participants received either ondansetron 16 mg per day or placebo for 10 weeks. The primary outcome variables were fatigue severity (Checklist Individual Strength fatigue severity subscale CIS-fatigue) and functional impairment (Sickness Impact Profile-8 SIP-8). The effect of ondansetron was assessed by analysis of covariance. Data were analyzed on an intention-to-treat basis. All patients were recruited between June 2003 and March 2006.
Thirty-three patients were allocated to the ondansetron condition, 34 to the placebo condition. The 2 groups were well matched in terms of age, sex, fatigue severity, functional impairment, and CDC symptoms. Analysis of covariance showed no significant differences between the ondansetron- and placebo-treated groups during the 10-week treatment period in fatigue severity and functional impairment.
This clinical trial demonstrates no benefit of ondansetron compared to placebo in the treatment of chronic fatigue syndrome.
www.trialregister.nl: ISRCTN02536681.
Aim: Ezetimibe administration with ongoing statin therapy is an effective option for further lowering low-density lipoprotein cholesterol (LDL-C) levels. Thus, we investigated the long-term efficacy ...and safety of fixed-dose combination of pitavastatin/ezetimibe (K-924 LD: 2mg/10mg; K-924 HD: 4mg/10mg). Methods: We conducted a phase III, multicenter, open-label trial involving patients with hypercholesterolemia receiving pitavastatin (2 or 4mg) who had not achieved their LDL-C management target. Patients were enrolled into the K-924 LD and HD groups based on whether they had received pitavastatin 2 and 4mg, respectively, and treated for 52 weeks. K-924 was administered orally once daily. The primary objective was to examine the percent change in LDL-C from baseline at week 52 with last observation carried forward imputation (LOCF) in all patients. Results: Of the 109 patients evaluated, 62 and 47 were assigned to the K-924 LD and HD groups, respectively. In all patients, LDL-C decreased by -30.3+-14.3% (p<0.001) from baseline (134.4+-37.9mg/dL). Consequently, 91.8% and 37.5% of the patients for primary and secondary prevention reached their LDL-C management target, respectively. These results were consistent in both the K-924 LD and HD groups. In the safety analysis, a single adverse drug reaction occurred in a patient in the K-924 HD group. Conclusion: After replacing pitavastatin monotherapy, K-924 was found to be effective and well-tolerated over 52 weeks. Thus, K-924 can contribute to intensifying LDL-C-lowering therapy without increasing the number of medications.
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